Process for the preparing bromoisophithalic acid compound

ABSTRACT

The present invention relates to a process for preparing bromoisophthalic acid compounds, particularly 5-bromoisophthalic acid compounds and 4,5-dibromoisophthalic acid compounds comprising brominating an isophthalic acid compound of the general formula (1) 
                 
 
wherein R 1  and R 2  independently of one another are hydrogen atom or C 1-6  alkyl, with bromine in a solvent containing sulfur trioxide. The object of the invention is to provide a process for preparing bromoisophthalic acid compounds, particularly 5-bromoisophthalic acid compounds and 4,5-dibromoisophthalic acid compounds in a highly selective manner by using bromine that is industrially inexpensive.

TECHNICAL FIELD

The present invention relates to a process for preparing abromoisophthalic acid compound comprising brominating an isophthalicacid compound of the general formula (1)

wherein R¹ and R² independently of one another are hydrogen atom or C₁₋₆alkyl. Bromoisophthalic acid compounds are key intermediates formodifiers for several polymers represented by polyesters and polyamides,etc. or functional chemicals, and pharmaceutical preparations andagricultural chemicals.

BACKGROUND ART

Conventionally, it is known that selective bromination of aromaticcompounds having an electron-attracting group is very difficult. Astechniques related to such a reaction, it is known, for example as amethod for preparing dialkyl 5-bromoisophtalate a method comprisingbrominating dimethyl isophthalate with bromine at the presence ofbromine trifluoride (BrF3) to give dimethyl 5-bromoisophtalate in a 55%yield (J. Org. Chem., 58, 239 (1993)). This method, however, usesbromine trifluoride that is expensive and intractable, and leads anaimed product in a low yield. Therefore, the above-mentioned method isnot practical.

An object of the present invention is to provide a process for preparingbromoisophthalic acid compounds, in particular 5-bromoisophthalic acidcompounds and 4,5-dibromoisophthalic acid compounds in a selectivemanner and a high yield, by the use of bromine that is inexpensiveindustrially.

As a result that the present inventors researched eagerly on processesfor preparing bromoisophthalic acid compounds and 4,5-dibromoisophthalicacid compounds can be prepared in a particularly selective manner and ahigh yield by the use of bromine that is inexpensive industrially, andcompleted the process for preparing bromoisophthalic acid compounds ofthe present invention.

DISCLOSURE OF INVENTION

That is, the present invention relates to a process for preparing abromoisophthalic acid compound comprising brominating an isophthalicacid compound of the general formula (1)

wherein R¹ and R² independently of one another are hydrogen atom or C₁₋₆alkyl, with bromine in a solvent containing sulfur trioxide.

It is very difficult to brominate compounds having anelectron-attracting group on its aromatic ring, such as isophthalicacid. Therefore, in the prior art, even if the reaction proceeds, itgives the corresponding compounds only in a low yield. The presentinventors found reaction conditions, such as the amount of sulfurtrioxide, reaction temperature and reaction time by which monobromo anddibromo products can be prepared in a high yield and a selective manner.

Hereinafter, the present invention will be described in detail.

Isophthalic acid compounds as a raw material are compounds of thegeneral formula (1)

wherein R¹ and R² independently of one another are hydrogen atom or C₁₋₆alkyl. R¹ and R² include specifically hydrogen, methyl, ethyl, n-propyl,i-propyl, n-butyl, i-butyl, s-butyl, t-butyl, 1-pentyl, 2-pentyl,3-pentyl, 3-methylbutyl, neopentyl, t-pentyl, 1-hexyl, 2-hexyl, 3-hexyl,1-methyl-1-ethylpropyl, 1,1,2-trimethyl propyl, 1,2,2-trimethyl propyl,3,3-dimethyl butyl and the like.

Further, the isophthalic acid compounds of the general formula (1)include isophthalic acid, or dialkyl isophthalate compounds, such asdimethyl isophthalate, diethyl isophthalate, methyl ethyl isophthalate,di-n-propyl isophthalate, di-i-propyl isophthalate, di-n-butylisophthalate, di-1-pentyl isophthalate, di-1-hexyl isophthalate,di-1-pentyl isophthalate and di-1-hexyl isophthalate. Among them,isophthalic acid and dimethyl isophthalates are preferable from thestandpoint of availability of industrial raw materials. Particularly,isophthalic acid is appropriate for a raw material in the presentreaction because it can be produced economically and its commercialproduct can be used at it is.

A characteristic of the present invention resides in bromination withbromine in a solvent containing sulfur trioxide. Conventionally, it isknown that compounds in which hydrogen atoms on the phenyl group aresubstituted with electron-attracting groups, such as isophthalic acidhardly reacts by the use of only bromine. The present inventorsattempted to an reaction with the bromine improved in its brominatingability by forming a complex between sulfur trioxide and bromine.Consequently, they found that monobromo products can be obtained, andfurther dibromo products also can be obtained by setting suitableconditions.

As the solvent containing sulfur trioxide, organic solvents can be used,but it is generally convenient to use sulfuric acid solvent, that isfuming sulfuric acid. Also, it is able to use chlorosulfonic acid,sulfur trioxide-dioxane complex, sulfur trioxide-pyridine complex or thelike that is a complex between sulfur trioxide and other compound. Amongthem, fuming sulfuric acid affords high reactivity in a reduced cost.

In a case where monobromo products are prepared, it is enough to usesulfur trioxide in an amount of number of moles no more than that ofbromine in order to obtain a high selectivity.

On the other hand, in a case where dibromo products are prepared, it isfavorable to use sulfur trioxide in an amount of number of moles no lessthan that of bromine.

On the form of fuming sulfuric acid, the concentration of sulfurtrioxide may be broadly selected, but commercially available productshaving a concentration of 10 to 60 wt % can be generally used. Also,fuming sulfuric acid having a concentration no more than 10 wt % can beprepared by adding sulfuric acid to the commercially available products.

Although the reaction is influenced by other conditions therefor, lowerconcentration (1 to 30 wt %) of sulfuric trioxide in fuming sulfuricacid is appropriate for preparing monobromo products, and higherconcentration thereof (10 to 60 wt %) is appropriate for preparingdibromo products.

As a solvent, hydrocarbon halides or sulfolane can be used besides theabove-mentioned sulfuric acid.

Concrete example of hydrocarbon halides include carbon tetrachloride,1,2-dichloroethane (EDC), 1,1,1-trichloroethane, 1,1,2-trichloroethaneand 1,1,2,2-tetrachloroethane. It is preferably appropriate to use it inan amount in weight of 1 to 20 times, particularly 2 to 10 times that ofsubstrate.

The brominating reaction of the present invention is characterized byusing bromine that is the most economic in industrial use. Commerciallyavailable bromine can be used as it is. The amount of bromine used ispreferably 0.5 to 1.5 time in moles that of substrate in a case wheremonobromo products are prepared, and preferably 1 to 3 times in molesthat of substrate in a case where dibromo products are prepared. In themeantime, the proportion of monobromo and dibromo products formed can beselected by sulfur trioxide concentration, reaction temperature andreaction time besides amount of bromine used.

It is necessary for the present reaction to be carried out with heating,and the reaction is carried out generally under pressure. The reactioncan be carried out at a temperature of 50° to 200° C., particularly 100°to 160°. The reaction time ranges generally from 1 to 100 hours althoughit changes depending on the kind of substrate, the amount of fumingsulfuric acid, the amount of bromine or the reaction temperature, andthe reaction ceases generally for 3 to 24 hours. In addition, the endpoint of the reaction can be confirmed by gas chromatography or liquidchromatography. The present reaction may be carried out in a batchsystem or a continuous system.

After the reaction is completed, a reaction solution is added into alarge excess of cooled water, and crystals separated out are filteredoff, washed with water and dried to give crude crystals of aimed bromoproducts. In addition, the crude crystals can be optionally purified byrecrystallization.

The present inventors examined several solvents for recrystallization,and consequently found that it is impossible for bromoisophthalic acidto be recrystallized with general solvents for recrystallization due toits slight solubility. On the contrary, the present inventors found thatlower alcohol solvents with 1 to 5 carbon atoms give aimed products inhigh yield of recrystallization and high purity. Among them,particularly methanol is preferable as the solvent as it exhibits goodability for recrystallization and advantage economically.

The present inventors found that a distillation method is applicable asanother method for purifying the bromo products produced by the presentinvention. That is, crude crystals of bromoisophthalic acid obtained bythe reaction are diesterified with a lower alcohol solvent with 1 to 5carbon atoms in the presence of an acid catalyst, and then the aimedbromo products can be separated from esters of unreacted raw materialsand other dibromo products by the use of distillation. As the acidcatalyst, sulfuric acid or p-toluene sulfonic acid can be used. It ispreferable to use the acid catalyst in an amount of 1 to 20 mol % basedon that of isophthalic acid compounds. On the other hand, among loweralcohol solvents with 1 to 5 carbon atoms, methanol or ethanol ispreferable from the standpoint of boiling point of the diesters. Theamount used thereof is generally 5 to 100 times in moles that ofisophthalic acid compounds.

The reaction can be generally carried out at a boiling point of analcohol used, but ceases for a short time by carrying out it at atemperature above the boiling point of the alcohol under pressure. In acase where methanol is used, the temperature is preferably 100° to 180°C.

It is preferable to carry out the reaction under reduced pressure aseach of the resulting esters has a high boiling point. Generally, it ispreferably carried out at 10 to 10000 Pa. Although simple distillationcan be carried out depending on the component of the reacted products,generally the aimed monobromo products with a high purity are obtainedby rectification.

Although dibromo products can be distilled out as faints after adistillation, they can be isolated by recrystallization of a stillresidue after monobromo products were distilled out.

In the meantime, when monobromo products are produced selectively, thereis a fear that dibromo products might be produced as the presentreaction is a successive reaction. Therefore, it is preferable torecycle raw materials by interrupting the reaction and making onlyisophthalic acid compounds and monobromo isophthalic acid compoundspresent in the reaction system. And, as mentioned above, anesterification with lower alcohol solvents with 1 to 5 carbon atoms iscarried out and then a distillation is carried out.

(R is lower alkyl with 1 to 5 carbon atoms.)

BEST MODE FOR CARRYING OUT THE INVENTION

Hereinafter, the present invention is described more concretely on thebasis of examples to which the present invention is not limited.

EXAMPLE 1

Into a 50 ml pressure and sealable glass tube, 1.66 g (10 mmol) ofisophthalic acid, 6.00 g of 10 wt % fuming sulfuric acid and 1.6 g (10mmol) of bromine were charged, and the content was stirred at 130° C.for 22 hours. After the conclusion of the reaction, the content wascooled to room temperature, and placed in a beaker containing ice waterto give a solid. The resulting solid was filtered off, washed withcooling, and further dried under reduced pressure to give 2.41 g(purity: 83.5%) of a crude crystal of the aimed product (yield: 81.9%).Then, the crystals were solved in 10 g of methanol at 60° C., cooled toroom temperature, and thereafter filtered off to give 1.61 g (purity:100%) of a white crystal (yield of recrystallization: 80.1%). Thiscrystal was identified as 5-bromopisophthalic acid by MASS, ¹H-NMR andmelting point.

EXAMPLES 2 to 7

Procedures were carried out similarly to that of Example 1 except thatthe reaction temperature, the concentration of fuming sulfuric acid andthe amount of bromine were changed. The results on the resultingmonobromo products were shown in Table 1.

TABLE 1 Concentration of Fuming Quantitative Yield (%) Ex. Sulfuric AcidBromine Tempera- Time 4,5- 2,5- No. (wt %)-(g) g(mmol) ture(° C.) (h.)5BIP IP DBIP DBIP 2 10-6 1.6(10) 110 22 34.5 58.0 trace — 3 20-6 1.6(10)110 22 48.6 43.2 trace — 4 30-6 1.6(10) 110 22 62.8 24.6 2.3 — 5 10-61.6(10) 150 22 77.0 4.1 8.0 — 6 20-6 1.6(10) 150 7 53.8 46.5 0.7 — 710-6 3.2(20) 150 7 79.1 6.4 5.8 trace IP: Isophthalic Acid,5BIP:5-Bromoisophthalic Acid, 4,5-DBIP: 4,5-Dibromoisophthalic Acid2,5-DBIP: 2,5-Dibromoisophthalic Acid

EXAMPLE 8

Into a 50 ml pressure and sealable glass tube, 1.66 g (10 mmol) ofisopthalic acid, 6.00 g of 30 wt % fuming sulfuric acid and 1.6 g (10mmol) of bromine were charged, and the content was stirred at 150° C.for 22 hours. After the conclusion of the reaction, the content wascooled to room temperature, and placed in a beaker containing ice waterto give a solid. Then, the resulting solid was filtered off, washed withcooling, and further purified by column chromatography on silica gel(chloroform/methanol=6/1, v/v) to give 0.51 g (yield: 20.7%) of5-bromoisophthalic acid, 0.76 g (yield: 23.5%) of 4,5-dibromoisophthalicacid and 0.07 g (yield: 2.1%) of 2,5-dibromoisophthalic acid. Thesecrystals were identified by MASS, ¹H-NMR and melting point.

EXAMPLES 9 to 16

Procedures were carried out similarly to that of Example 8 except thatthe reaction temperature, the concentration of fuming sulfuric acid andthe amount of bromine were changed. The results on the resultingmonobromo and dibromo products were shown in Table 2.

TABLE 2 Concentration of Fuming Quantitative Yield (%) Ex. Sulfuric AcidBromine Tempera- Time 4,5- 2,5- No. (wt %)-(g) g(mmol) ture(° C.) (h.)5BIP IP DBIP DBIP 9 60-6  1.6(10) 110 22 45.0 1.4 18.7 1.0 10 20-6 1.6(10) 130 22 49.2 0.0 15.3 trace 11 30-6  1.6(10) 130 22 53.1 0.8 13.61.0 12 20-6  1.6(10) 150 22 43.1 0.0 20.0 0.8 13 20-6  3.2(20) 150 737.5 0.0 23.3 1.5 14 10-12 1.6(10) 150 7 47.0 0.6 18.1 1.2 15 20-121.6(10) 150 7 49.8 0.7 20.3 1.4 16 20-12 3.2(10) 150 7 11.9 0.0 26.2 4.9IP: Isophthalic Acid, 5BIP:5-Bromoisophthalic Acid, 4,5-DBIP:4,5-Dibromoisophthalic Acid 2,5-DBIP: 2,5-Dibromoisophthalic Acid

EXAMPLE 17

Into a 50 ml pressure and sealable glass tube, 1.66 g (10 mmol) ofisopthalic acid, 6.00 g of 10 wt % fuming sulfuric acid and 1.6 g (10mmol) of bromine were charged, and the content was stirred at 150° C.for 7 hours. After the conclusion of the reaction, the content wascooled to room temperature, and placed in a beaker containing ice waterto give a solid. The resulting solid was filtered off, washed withcooling, and further dried under reduced pressure to give a crudecrystal of the aimed product. Then, dimethyl esters were derived fromthe crystal by heating and stirring it at 120° C. with 13.1 g (408 mmol)of methanol and 0.35 g (30 mol %) of sulfuric acid in an autoclave. Insuccession, the esters were subjected to rectification to give 1.78 g(yeild: 65.1%, vacuum boiling point: 159° C./4.8 mmHg) of aimed dimethyl5-bromoisophthalate and 0.52 g (yield: 26.8%, vacuum boiling point: 133°C./4.8mmHg) of dimethyl isophthalate corresponding to a raw material.The resulting crystals were identified as dimethyl 5-bromoisophthalateand 5-bromoisophthalic acid by MASS, ¹H-NMR and melting point.

EXAMPLE 18

Into a 100 ml pressure and sealable glass tube, 9.70 g (50 mmol) ofdimethyl isophthalate, 30.00 g of 10 wt % fuming sulfuric acid and 10.40g (100 mmol) of bromine were charged, and the content was stirred at120° C. for 7 hours. After the conclusion of the reaction, the contentwas cooled to room temperature, and placed in a beaker containing icewater to give a solid. The resulting solid was filtered off, washed withcooling, and further dried under reduced pressure to give 11.95 g of acrude crystal of the aimed product (reaction yield: 50.4%5-bromoisophthalic acid, 19.6% isophthalic acid, 4.9%2,5-dibromoisophthalic acid, 7.2% 4,5-dibromoisophthalic acid, 7.0%dimethyl 5-bromoisophthalate, 1.5% dimethyl isophthalate, 0.9% dimethyl2,5-dibromoisophthalate and 0.2% dimethyl 4,5-dibromoisophthalate).Then, dimethyl esters were derived from the crystal by heating andstirring it with 65.50 g (2.04 mol) of methanol and 1.75 g (30 mol %) ofsulfuric acid in an autoclave at 120° C.

In succession, the esters were subjected to rectification to give 6.73 g(yield: 49.3%, vacuum boiling point: 159° C./4.8mmHg) of aimed dimethyl5-bromoisophthalate and 1.67 g (yield: 17.2%, vacuum boiling point: 133°C./4.8mmHg) of dimethyl isophthalate corresponding to a raw material.The resulting crystals were identified as dimethyl 5-bromoisophthalateand 5-bromoisophthalic acid by MASS, ¹H-NMR and melting point.

Industrial Applicability

According to the process of the present invention, 5-bromoisophthalicacid compounds can be prepared in a selective manner and a reduced cost.

1. A process for preparing 5-bromoisophthalic acid compound comprisingbrominating an isophthalic acid compound of the general formula (1)

wherein R¹ and R² independently of one another are hydrogen atom or C₁₋₆alkyl, with bromine in fuming sulfuric acid containing sulfur trioxidein a concentration of 1 to 30 wt % at a reaction temperature between100° and 160° C.
 2. A process for preparing 5-bromoisophthalic aciddiester compound comprising the steps of: brominating an isophthalicacid compound of the general formula (1)

wherein R¹ and R² independently of one another are hydrogen atom or C₁₋₆alkyl, with bromine in a molar amount 0.5 to 1.5 times that of theisophthalic acid compound in fuming sulfuric acid containing sulfurtrioxide in a concentration of 1 to 30 wt % at a reaction temperaturebetween 100° C. and 160° C. to produce a crude product; diesterifyingthe resulting crude product with a lower alcohol with 1 to 5 carbonatoms at the presence of an acid catalyst to a diesterified compound;and then separating and purifying the diesterified compound bydistillation.
 3. The process for preparing 5-bromoisophthalic aciddiester compound according to claim 2, wherein the acid catalyst issulfuric acid, and the diesterification is carried out under pressure ata reaction temperature above the boiling point of the lower alcohol with1 to 5 carbon atoms.
 4. The process for preparing 5-bromoisophthalicacid diester compound according to claim 2, wherein the lower alcoholwith 1 to 5 carbon atoms is methanol or ethanol.